High-Resolution Mapping of Protein Concentration Reveals Principles of Proteome Architecture and Adaptation

• Published in: Cell reports (Cambridge) Vol. 7; no. 4; pp. 1333 - 1340
• Main Authors: Levy, Emmanuel D., Kowarzyk, Jacqueline, Michnick, Stephen W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.05.2014; Elsevier
• Subjects: Protein Interaction Mapping; Proteome - metabolism; Proteomics - methods; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2014.04.009

A single yeast cell contains a hundred million protein molecules. How these proteins are organized to orchestrate living processes is a central question in biology. To probe this organization in vivo, we measured the local concentration of proteins based on the strength of their nonspecific interactions with a neutral reporter protein. We first used a cytosolic reporter and measured local concentrations for ∼2,000 proteins in S. cerevisiae, with accuracy comparable to that of mass spectrometry. Localizing the reporter to membranes specifically increased the local concentration measured for membrane proteins. Comparing the concentrations measured by both reporters revealed that encounter frequencies between proteins are primarily dictated by their abundances. However, to change these encounter frequencies and restructure the proteome, as in adaptation, we find that changes in localization have more impact than changes in abundance. These results highlight how protein abundance and localization contribute to proteome organization and reorganization. [Display omitted] •The authors present a strategy to measure local protein concentration in vivo•Measurements correlate with local cytosol and membrane protein concentrations•Abundance dominates random protein-encounter frequencies in the cell•Localization dominates changes in random protein-encounter frequencies Levy et al. now show that the local concentration of proteins can be accurately measured through the strength of their nonspecific interactions with an in vivo reporter. By localizing the reporter in S. cerevisiae, the authors measure local protein concentrations both at the membrane and in the cytosol. Comparing these concentrations for over 2,000 proteins reveals that the heterogeneity of protein encounter frequencies is dominated by the heterogeneity of absolute abundances. Yet, in modulating these encounter frequencies, changes in localization have a greater impact than changes in abundance.